We propose to test the hypothesis that accumulation of altered proteins due to reduced protein turnover is causally related to dysfunctions associated with aging in the soil nematode, Caenorhabditis elegans. We will identify, purify and characterize the major lysosomal endoproteases, and isolate mutants altered in each of them. Mutants altered in protein turnover will also be isolated and characterized. Using these two groups of mutants, as well as specific enzyme inhibitors, we will then modulate the rate of protein turnover in vivo and assess the effects of such modulation on the accumulation of altered (damaged) proteins, on other age-dependent functional changes, and on lifespan. The age-dependence of endoprotease activities and of protein turnover will also be examined in wild-type C. elegans.